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Hypoxia-Inducible Factors: Mediators of Cancer Progression; Prognostic and Therapeutic Targets in Soft Tissue Sarcomas

Anatomic Pathology, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 3400 Spruce Street, 6th Floor Founders Building, Philadelphia, PA 19104, USA
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Cancers 2013, 5(2), 320-333; https://doi.org/10.3390/cancers5020320
Received: 23 January 2013 / Revised: 12 March 2013 / Accepted: 26 March 2013 / Published: 2 April 2013
(This article belongs to the Special Issue Soft Tissue and Bone Sarcoma)
Soft-tissue sarcomas remain aggressive tumors that result in death in greater than a third of patients due to either loco-regional recurrence or distant metastasis. Surgical resection remains the main choice of treatment for soft tissue sarcomas with pre- and/or post-operational radiation and neoadjuvant chemotherapy employed in more advanced stage disease. However, in recent decades, there has been little progress in the average five-year survival for the majority of patients with high-grade soft tissue sarcomas, highlighting the need for improved targeted therapeutic agents. Clinical and preclinical studies demonstrate that tumor hypoxia and up-regulation of hypoxia-inducible factors (HIFs) is associated with decreased survival, increased metastasis, and resistance to therapy in soft tissue sarcomas. HIF-mediated gene expression regulates many critical aspects of tumor biology, including cell survival, metabolic programming, angiogenesis, metastasis, and therapy resistance. In this review, we discuss HIFs and HIF-mediated genes as potential prognostic markers and therapeutic targets in sarcomas. Many pharmacological agents targeting hypoxia-related pathways are in development that may hold therapeutic potential for treating both primary and metastatic sarcomas that demonstrate increased HIF expression. View Full-Text
Keywords: soft tissue sarcoma; hypoxia; hypoxia-inducible factor; HIFs soft tissue sarcoma; hypoxia; hypoxia-inducible factor; HIFs
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MDPI and ACS Style

Sadri, N.; Zhang, P.J. Hypoxia-Inducible Factors: Mediators of Cancer Progression; Prognostic and Therapeutic Targets in Soft Tissue Sarcomas. Cancers 2013, 5, 320-333.

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